Recent studies in several models of pain have shown that significant reduction in the pain response can be achieved using MetaPhore's proprietary SuperOxide Dismutase mimetics. One of these, M40403, a highly active and selective SOD catalyst possessing 'in vivo' stability, is highly effective in attenuating the pain response. Baked on our observations that superoxide may play a critical role in pain of various etiologies and that such selective SOD catalysts do attenuate pain, we propose to develop a SOD mimetic of the M40403 class as a novel parenteral non-narcotic analgesic for the treatment of pain. Given the need for better pain management and the novel nature of our findings, we propose to move the program aggressively forward to the clinic and are, consequently, submitting this grant for consideration as a fast track Phase I/II grant. The Phase I portion is focused on continuing to develop our mechanistic understanding of the role of superoxide in pain, to evaluate a second SOD mimetic in pain models, to determine the potential clinical advantage of synergistic interaction of our SOD mimetics with opiates and non-steroidal anti-inflammatory drugs for pain relief, and to explore the potential of the SOD mimetics for pain management. PROPOSED COMMERCIAL APPLICATIONS: The pain market is served by products with major limitations, leading to serious undermedication. Pending federal legislation, the 'Pain Relief Promotion Act', is designed to encourage physicians to treat pain more aggressively by providing legal protection from unintended side effects. This encourages the development of novel pain medications with reduced side effects. Initial animal tests show that SOD mimetics have novel and powerful analgesic properties giving rise to expectations that these compounds have very large commercial potential.